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A histologic demonstration of siliceous materials in simian lung mite infected lung tissues by microincineration.

Approximately 90% of freshly imported macaques and other Old World Monkeys are known to be infected with respiratory mites. The lung associated pigments are integral components of pulmonary acariasis in Old World Monkeys; at least three distinctive pigmental bodies are identified in association with lung mite infection. Two major components of pigments are recently identified as silica by using elemental analysis using a high voltage electron microscope and an energy-dispersive X-ray analysis technique. Since a limited number of infected monkey lung tissues and associated pigments can be examined by this tedious procedure, it was important for us to examine much greater number of specimens to verify our initial observation. Ten microincineration technique described provided a unique and practical way to identify the mineral elements in as many 27 histologic sections within a short span of time. Silica and silicates are heat resistant whereas majority of organic materials including lung mite parasites disintegrated under the extreme temperature. Mineral elements were exclusively located within the polarizable white ash. More than 90% of total pigmental bodies identified were found to be related to siliceous materials in 20 incinerated infected monkey lung tissues whereas five noninfected lungs similarly examined did not reveal any pigmental bodies. Other than a small of fine granular mucin substances which were PAS positive, the majority of lung mite associated pigments such as large granules of hemosiderin, needle-like crystals and other fine granules engulfed by macrophages were identified to be siliceous materials as they have persisted even after microincineration. Mite parasites and other organic materials were completely disintegrated. Similar pigmental bodies examined by microscope X-ray analysis were positive for silicate. This finding suggests that lung mite infection in Old Monkeys apparently predisposed silicosis. Therefore, until the link between lung mite infection and silicosis is clarified, experimental inhalation toxicologic findings in mite-infected Old World monkeys should be interpreted cautiously.

Animals↗

Pyogenic lung infections.

Pyogenic lung infections still occur despite the availability of effective antibiotics for the treatment of patients with acute bacterial pneumonia. Our understanding of the pathogenesis and management of these conditions has steadily improved over the past few decades, although some areas remain obscure. The effect of HIV infection on the incidence of pyogenic lung infections remains largely unknown, and large studies are required to evaluate this. Burkholderia (formerly Pseudomonas) cepacia strains are now recognized as important respiratory pathogens in patients with cystic fibrosis, and the high transmissibility of some strains, combined with their inherent multiple antibiotic resistance, are continuing causes for concern.

AIDS-Related Opportunistic Infections↗

Expression of mast cell proteases in rat lung during helminth infection: mast cells express both rat mast cell protease II and tryptase in helminth infected lung.

BACKGROUND: The phenotype of proliferated mast cells in Nippostrongylus brasiliensis-infected rat lung has been identified as mucosal mast cells (MMC) but not connective tissue mast cells (CTMC). However, a previous study of ours showed that the expression of rat mast cell tryptase (RMCT) mRNA, which has been reported to be confined to CTMC, significantly increased in rat lung 14 days after infection. METHODS: The expression of four mast cell proteases in rat lung during the course of infection with N. brasiliensis was examined by RNA blot analysis. Immunohistochemical analysis of RMCT and rat mast cell protease (RMCP) II, which has been reported to be confined to MMC was also performed. RESULTS: The number of lung mast cells did not change until 7 days after infection, then gradually increased until 21 days after infection. The expression of the RMCP II gene had increased 14 and 21 days after infection. In addition, the expression of the RMCP I and RMCT genes had also increased at the same time points, but RMCP III had not. By immunohistochemistry, most of the mast cells in infected lung were identified as RMCP II+/RMCT- (MMC), but both RMCP II+ and RMCT+ mast cells were also observed. CONCLUSIONS: The present results suggest that mast cell phenotype alteration or a distinct mast cell subset might be present in N. brasiliensis-infected rat lung, and therefore N. brasiliensis-infected rat lung may be a useful tool for studying the differentiation mechanism of mast cells.

Animals↗

Experimental ventilator-associated pneumonia: distribution of lung infection and consequences for lung aeration.

Ventilator-associated pneumonia (VAP) has been described in humans and in experimental animals. The most severe lesions are located in dependent lung segments along a sterno-vertebral axis, however the cephalocaudal distribution of lung infection remains unknown. We used an experimental model to evaluate the distribution of lung infection, considering its anteroposterior and cephalocaudal gradient, and its impact on lung aeration. Ten healthy domestic piglets were anesthetized, paralyzed and mechanically ventilated for 59 hours in the prone position. At the end of the experiment they were sacrificed and their lungs were fixed. Six segments were analyzed: a non-dependant (ND) and a dependant (D) segment of the upper (UL), middle (ML) and lower (LL) lobes. The presence of healthy lung or of histological infectious lesions was analyzed with a semi-quantitative method. The regional distribution of lung infection was compared between upper, middle and lower lobes, as well as between dependant and non-dependant regions. The presence of infectious lesions was correlated with measurements of lung aeration. Nine of the ten piglets developed VAP. Infectious lesions were distributed along a sterno-vertebral and a cephalocaudal gradient; the lower and middle lobes were more frequently infected than the upper lobes. There was an inverse correlation (R= - 0.902) between the development of lung lesions and lung aeration. In conclusion, VAP was a frequent complication in healthy mechanically ventilated piglets, showing an anteroposterior as well as a cephalocaudal gradient. As expected, development of lung infection was accompanied by a corresponding loss of aeration.

Animals↗

Antibodies against beta-lactamase can improve ceftazidime treatment of lung infection with beta-lactam-resistant Pseudomonas aeruginosa in a rat model of chronic lung infection.

To test the hypothesis that antibodies against the chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) might act as beta-lactamase inhibitors in patients with cystic fibrosis and chronic lung infection with P. aeruginosa, we compared in a rat model of chronic lung infection the efficacy of treatment with ceftazidime in beta-lactamase-immunized (group I) and non-immunized (group II) rats. Chronic lung infection was established with alginate-embedded P. aeruginosa producing high amounts of beta-lactamase in 133 Lewis rats. Prior to infection, group I (66 rats) was immunized three times at 2-week intervals with purified beta-lactamase in incomplete Freund's adjuvant (IFA) and group II (67 rats) received IFA. Ceftazidime treatment was initiated after challenge and continued for 10 days, after which the rats were sacrificed and the lung bacteriology and pathology were analysed. Rat serum was analysed for the beta-lactamase inhibitory activity and a beta ab-specific IgG and IgG subclasses titres. Beta-lactamase inhibitory activity was found only in sera of rats belonging to group I and it was used to divide these rats into two subgroups: rats whose sera inhibited > or = 75% of beta-lactamase activity (responders) and rats whose sera inhibited < or = 25% of beta-lactamase activity (non-responders). The responder subgroup had significantly smaller pathological areas in the lungs and lower cfu/ml lung homogenate compared to the non-immunized group (p=0.02 and p=0.01, respectively) and compared to the non-responder subgroup (p=0.008 and p=0.0001, respectively). On the day of challenge, significantly higher titres of a beta ab-specific IgG and IgG subclasses antibodies were found in the responders compared to the non-responders (p<0.0001). In the responder subgroup the avidity of IgG a beta ab was significantly higher than in the non-responder subgroup (p=0.0003). Our study showed that a beta ab with beta-lactamase inhibitory activity raised by immunization with beta-lactamase can improve the outcome of treatment with ceftazidime of resistant P. aeruginosa in a rat model of chronic lung infection.

Animals↗

Lung infections in pediatric lung transplantation: experience in 49 cases.

OBJECTIVES: Pulmonary infections, and particularly cytomegalovirus (CMV) infections, are a major cause of morbidity after lung transplantation. We report here our results in 49 pediatric lung transplantations. METHODS: Between may 1988 and 1997, we have done 49 lung transplantations in 42 children (en bloc double lung transplantation (DLT):10, HLTx:7, sequential bilateral sequential-lung transplantation (BSLT):31, single-lung transplantation (SLT): 1). In seven, it was a retransplantation. Among these, 34 were cystic fibrosis (CF) patients, all with multiresistant organisms (Pseudomonas aeruginosa, Burkholderia cepacia, Achromobacter xylososydans, Staphylococcus aureus). All patients were treated with multiantibiotic prophylaxy adapted to the preoperative cultures. Donor-recipient CMV matching was possible in only 31 cases. CMV prophylaxy and immunosuppression protocols have evolved with time, with a current protocol of IV Gancyclovir prophylaxy for 3 months and triple drug immunosuppression without post-operative rabbit anti-thymocyte globulin (RATG) induction. There was no perioperative mortality in the primary transplantations and three early deaths in the whole group (6.1%). RESULTS: Only five patients had no pulmonary infection. The patients presented 3.2 infection episodes per year, 75% localized on the lungs, 41% during the first 3 months. Among the 13 deaths in the 1st year, 10 were directly related to infection, 60% due to CMV. After the 1st year, in all patients dying of pulmonary dysfunction or obliterative bronchiolitis (OB), bacterial infections were associated. There was no serious fungal infection. Actuarial survival at 3 months, 1, 3, 5 years were 85, 65.7, 47.5 and 28.5%, respectively. There was a significant difference in 3 year survival between patients receiving CMV negative organs (40%) and CMV positive organs (17%). CONCLUSION: In our experience, as in other's, pulmonary infection risk is important in lung transplantation. Bacterial infections were mainly an aggravating factor of secondary pulmonary dysfunction or OB, and were not the primary cause of death. CMV infections have been very severe and lead us, despite the scarcity of donors, to avoid positive donors in negative recipients, this leads to disastrous mid-term results in our experience, despite prophylaxis.

Adolescent↗

Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis. A longitudinal study of immune complex activity and inflammatory response in sputum sol-phase of cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infections: influence of local steroid treatment.

A double blind controlled trial of Becotide (beclomethasone diproprionate) inhalations was carried out for treating cystic fibrosis patients with chronic P. aeruginosa lung infection to determine its efficacy and safety. The aim of the treatment was to diminish the inflammatory response in the lungs of these patients, a response which is initiated by an allergic type III reaction. Pulmonary inflammation was evaluated by measurements of proteolytic activity, albumin concentration and immune complex activity in the sputum sol-phase before, during, and after the 16 weeks the trial lasted. 26 cystic fibrosis patients participated (13 received Becotide and 13 placebo) and the results showed that local steroids have no effect on the inflammatory response in the lungs of cystic fibrosis patients with chronic P. aeruginosa lung infection. No adverse effects were demonstrated. There was, however, a significant increase in the inflammatory parameters for all 26 cystic fibrosis patients when the trial period was over, compared to the insidious pulmonary destruction which takes place in the lungs of these patients, and it corresponded to a significant decrease (p less than 0.05) in forced vital capacity which took place at the same time. Therefore, chronic P. aeruginosa lung infection in these patients should be treated as efficiently as possible.

Adolescent↗

[Primary infection type atypical mycobacteriosis (lung infection) in the Fuji City Central Hospital during 1989-94].

A Clinical observation was carried out on primary infection type atypical mycobacteriosis (lung infection) in the Fuji City Central Hospital (Fuji-shi, Shizuokaken, Japan) during 1989-94. 1) Twenty-five out of 118 cases (21.8%) admitted to the tuberculosis ward of the hospital were atypical mycobacteriosis. Ten out of 25 cases with atypical mycobacteriosis were primary infection (8.5%). 2) The results of identification of atypical mycobacteria isolated from cases were as follows: M. avium-intracellulare complex: 4 cases M. kansasii: 3 cases M. scrofulaceum: 2 cases Unknown: 1 case 3) Background factor of atypical mycobacteriosis was observed in 6 out of 10 cases. No background factor was seen in 4 cases. 4) In spite of resistance to drugs of isolated mycobacteria in vitro, treatment by drugs such as INH, RFP, and SM was effective in clinical course. That is, mycobacteria in sputum converted to negative, and chest X-ray shadow improvement.

Adult↗

Gerimax ginseng regulates both humoral and cellular immunity during chronic Pseudomonas aeruginosa lung infection.

BACKGROUND: Chronic lung infection among patients with cystic fibrosis (CF), diffused panbronchiolitis, and chronic obstructive bronchiecteisis is often because of Pseudomonas aeruginosa. High morbidity and mortality in patients with CF are because of P. aeuruginosa that undergoes genotypic and phenotypic changes during prolonged stay in the lung resulting in increased antibiotic resistance, necessitating a search for alternative or supplement drugs. OBJECTIVE: In this study we compared the therapeutical effect of Gerimax (Dansk Droge A/S, Ishøj, Denmark) ginseng with placebo control by using a rat model of chronic P. aeruginosa lung infection mimicking that in patients with CF. METHODS AND INTERVENTIONS: The animals were challenged intratracheally with the prototypic P. aeruginosa PAO1 in alginate beads (1 x 10(9) colony-forming units per milliliter [CFU/mL]) followed by subcutaneous injection of ginseng extract (150 mg/kg body weight once per day) and examined on days 7 and 21. RESULTS: The day 7 analyses show that ginseng treatment resulted in lowering serum immunoglobulin M (IgM) and lung interleukin-4 (IL-4) levels compared to the control group. On day 21, higher lung IgA, upregulated serum IgG2a, stronger lung responses of interferon-gamma, IL-4, and tumor necrosis factor-alpha with milder lung pathology and enhanced lung bacteriology were detected in the ginseng-treated group when compared to those of the control group. CONCLUSION: These results suggest that the Gerimax ginseng treatment can modulate the immune system in favor of clearing the infection with P. aeruginosa in the lungs of rats. Thus, ginseng might be a promising alternative supplement for the treatment of chronic P. aeruginosa lung infection in patients with CF.

Animals↗

[A case of Mycobacterium scrofulaceum lung infection occurring in old lung tuberculosis lesion].

A 68-year-old man was admitted because of a persistent productive cough of 6 weeks' duration and detection of acid-fast bacilli from sputum. Based on chest roentgenograms and isolation of Mycobacterium scrofulaceum from sputum, on admission, a diagnosis of Mycobacterium scrofulaceum lung infection was made. Although the organisms were resistant to 0.1 microgram/ml of INH, 2.5 micrograms/ml of EB and 10 micrograms/ml of RFP, sputum converted to negative by the use of INH (0.4 g/day), EB (0.5 g/day) and RFP (0.3 g/day) for 2 months. The incidence rate of nontuberculous lung mycobacteriosis seems to be increasing recently. This is partially considered to be due to an increase of various strains of nontuberculous mycobacteria in the environment. A striking advance of clinical medicine and changes in the constitution of human society and environment surrounding us produce an increase in the number of compromised hosts. The lung disease due to Mycobacterium scrofulaceum, a kind of opportunistic pathogen, is considered to be increasing in a wide variety of compromised hosts in the future.

Aged↗

Effects of intratracheal administration of novispirin G10 on a rat model of mucoid Pseudomonas aeruginosa lung infection.

Chronic Pseudomonas aeruginosa lung infection is a major problem for patients with cystic fibrosis (CF). The biofilm mode of growth of the pathogen makes it highly resistant to antibiotic treatment, and this is especially pronounced with mucoid strains. In this study, novispirin G10, a synthetic antimicrobial peptide patterned loosely on sheep myeloid antimicrobial peptide 29, was tested in a rat model of mucoid P. aeruginosa lung infection. P. aeruginosa NH57388A, a mucoid strain isolated from a CF patient, was mixed with the alginate produced by the bacterium itself and adjusted to a concentration of 10(10) CFU/ml. Each rat received 10(9) CFU of bacteria intratracheally in the left lung to establish lung infection. At 0 and 3 h post P. aeruginosa infection, the treated group of rats received novispirin G10 (0.1 mg/ml, 0.1 ml/rat) intratracheally, whereas the control group received vehicle treatment only. The animals were sacrificed on days 3, 5, 7, and 10 after challenge for evaluation of various parameters. On day 5, 50% of the rats in the treated group had cleared the bacteria from the lungs, whereas in the control group, none of the rats cleared the pathogen (P < 0.03). The average bacterial loads remaining in the lungs of treated rats on days 3 and 5 were more than 170- and 330-fold lower than in the control groups (P < 0.0005 and P < 0.0003). In accordance, the macroscopic and microscopic lung pathology was also significantly milder in the treated group compared to the control group (P < 0.0002). Lung cytokine responses in the treated group were significantly lower than in the control group. The results suggest that novispirin G10 might be useful in treating antibiotic-resistant P. aeruginosa lung infections.

Animals↗